This program project examines the structure, biosynthesis, and roles of carbohydrates in cell-cell interaction. The proposed projects were borne-out from our strong collaborative research activities in the previous funding period. This program project is a continued close collaboration among investigators whose expertise ranges from carbohydrate synthetic chemistry, carbohydrate biosynthesis, immunology, to cellular and molecular biology. In the coming years, we will add strength in research capability by incorporating intravital microscopy to observe migrating and interacting cells in vivo. The work centers around sulfated, fucosylated glycoconjugates in lymphocyte trafficking, tumor progression, and myelopoiesis. The work includes the role of carbohydrate-mediated signal transduction, a novel aspect in the field, through studies on the role of fucose in Notch signaling. The work also determines the role of carbohydrate-dependent tumor metastasis by identifying novel carbohydrate recognition molecules and their use for tumor targeting, and determining the roles of heparan sulfate in tumor angiogenesis. These studies will provide new information on the roles of carbohydrates in myelopoiesis, chronic inflammation, tumor progression, and carbohydrate-dependent signal transduction. The knowledge gained from these studies may help in the design of improved therapeutic intervention against malignancies and other diseases.